The Receptor Protein Tyrosine Phosphatase, PTP-RO, Is Upregulated During Megakaryocyte Differentiation and Is Associated With the c-Kit Receptor
In: Blood, Jg. 94 (1999-07-15), S. 539-549
Online
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Zugriff:
We have recently isolated a cDNA encoding a novel human receptor-type tyrosine phosphatase, termed PTP-RO (for a protein tyrosine phosphatase receptor omicron), from 5-fluorouracil–treated murine bone marrow cells. PTP-RO is a human homologue of murine PTPλ and is related to the homotypically adhering κ and μ receptor-type tyrosine phosphatases. PTP-RO is expressed in human megakaryocytic cell lines, primary bone marrow megakaryocytes, and stem cells. PTP-RO mRNA and protein expression are upregulated upon phorbol 12-myristate 13-acetate (PMA) treatment of the megakaryocytic cell lines CMS, CMK, and Dami. To elucidate the function of PTP-RO in megakaryocytic cells and its potential involvement in the stem cell factor (SCF)/c-Kit receptor pathway, COS-7 and 293 cells were cotransfected with the cDNAs of both the c-Kit tyrosine kinase receptor and PTP-RO. PTP-RO was found to be associated with the c-Kit receptor in these transfected cells and the SCF/Kit ligand induced a rapid tyrosine phosphorylation of PTP-RO. Interestingly, these transfected cells demonstrated a decrease in their proliferative response to the SCF/Kit ligand. In addition, we assessed the association of PTP-RO with c-Kit in vivo. The results demonstrated that PTP-RO associates with c-Kit but not with the tyrosine kinase receptor FGF-R and that PTP-RO is tyrosine-phosphorylated after SCF stimulation of Mo7e and CMK cells. Antisense oligonucleotides directed against PTP-RO mRNA sequences significantly inhibited megakaryocyte progenitor proliferation. Therefore, these data show that the novel tyrosine kinase phosphatase PTP-RO is involved in megakaryocytopoiesis and that its function is mediated by the SCF/c-Kit pathway.
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The Receptor Protein Tyrosine Phosphatase, PTP-RO, Is Upregulated During Megakaryocyte Differentiation and Is Associated With the c-Kit Receptor
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Autor/in / Beteiligte Person: | Taniguchi, Yoshitaka ; London, Roanna ; Jiang, Shuxian ; Avraham, Hava ; Schinkmann, Karin |
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Zeitschrift: | Blood, Jg. 94 (1999-07-15), S. 539-549 |
Veröffentlichung: | American Society of Hematology, 1999 |
Medientyp: | unknown |
ISSN: | 1528-0020 (print) ; 0006-4971 (print) |
DOI: | 10.1182/blood.v94.2.539.414k40_539_549 |
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